{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:43:51Z","timestamp":1793839431329,"version":"4.6.1"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The complement system (C) is a crucial component of the innate immune system. An increasing body of research has progressively shed light on the pivotal role of C in immunological tolerance at the feto-maternal interface. Excessive C activation or impaired C regulation may determine the onset of pregnancy-related pathological conditions, including pre-eclampsia (PE). Thus, several studies have investigated the presence of C components or split products in blood matrixes (<jats:italic>i.e.<\/jats:italic>, plasma, serum), urine, and amniotic fluid in PE. In the current study, we systematically reviewed the currently available scientific literature reporting measurements of C components as circulating biomarkers in PE, based on a literature search using Pubmed, Scopus, and Embase databases. A total of 41 out of 456 studies were selected after full-text analysis. Fourteen studies (34.1%) were identified as measuring the blood concentrations of the classical pathway, 5 (12.1%) for the lectin pathway, 28 (68.3%) for the alternative pathway, 17 (41.5%) for the terminal pathway components, and 16 (39%) for C regulators. Retrieved results consistently reported C4, C3, and factor H reduction, and increased circulating levels of C4d, Bb, factor D, C3a, C5a, and C5b-9 in PE compared to normal pregnancies, depicting an overall scenario of excessive C activation and aberrant C regulation. With evidence of C activation and dysregulation, C-targeted therapy is an intriguing perspective in PE management. Moreover, we also discussed emerging pitfalls in C analysis, mainly due to a lack of experimental uniformity and biased cohort selection among different studies and laboratories, aiming to raise a more comprehensive awareness for future standardization.<\/jats:p><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p><jats:uri>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:uri>, identifier CRD42024503070.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1419540","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T04:33:11Z","timestamp":1719203591000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Systematic review of the complement components as potential biomarkers of pre-eclampsia: pitfalls and 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